Abstract | PURPOSE: MATERIALS AND METHODS: RESULTS: Moderate or strong phospho-S6 immunoreactivity was found in 17 of 29 clear cell carcinomas (59%), of which 14 were also moderately/strongly positive for phospho-mTOR (Ser2448). We hypothesized that this activation of the mTOR signaling pathway in clear cell renal cell carcinoma could reflect mutational activation of Rheb or RhebL1, which are Ras family members that directly activate mTOR. However, no mutations in exons 3 and 4 (homologous sites of Ras activating mutations) in Rheb or RhebL1 were identified. Two of 3 renal clear cell carcinoma derived cell lines also showed inappropriate S6 hyperphosphorylation. Treatment of all 3 cell lines with rapamycin significantly decreased S6 phosphorylation and proliferation. CONCLUSIONS:
|
Authors | Victoria A Robb, Magdalena Karbowniczek, Andres J Klein-Szanto, Elizabeth P Henske |
Journal | The Journal of urology
(J Urol)
Vol. 177
Issue 1
Pg. 346-52
(Jan 2007)
ISSN: 0022-5347 [Print] United States |
PMID | 17162089
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Chemical References |
- Protein Kinases
- MTOR protein, human
- TOR Serine-Threonine Kinases
|
Topics |
- Carcinoma, Renal Cell
(chemistry, genetics)
- Humans
- Immunohistochemistry
- Kidney Neoplasms
(chemistry, genetics)
- Protein Kinases
(analysis, genetics, physiology)
- TOR Serine-Threonine Kinases
- Tumor Cells, Cultured
|